Article

Hyperpolarized C-13 Spectroscopic Imaging Informs on Hypoxia-Inducible Factor-1 and Myc Activity Downstream of Platelet-Derived Growth Factor Receptor

Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94158, USA.
Cancer Research (Impact Factor: 9.28). 10/2010; 70(19):7400-10. DOI: 10.1158/0008-5472.CAN-10-0883
Source: PubMed

ABSTRACT The recent development of hyperpolarized (13)C magnetic resonance spectroscopic imaging provides a novel method for in vivo metabolic imaging with potential applications for detection of cancer and response to treatment. Chemotherapy-induced apoptosis was shown to decrease the flux of hyperpolarized (13)C label from pyruvate to lactate due to depletion of NADH, the coenzyme of lactate dehydrogenase. In contrast, we show here that in PC-3MM2 tumors, inhibition of platelet-derived growth factor receptor with imatinib reduces the conversion of hyperpolarized pyruvate to lactate by lowering the expression of lactate dehydrogenase itself. This was accompanied by reduced expression of vascular endothelial growth factor and glutaminase, and is likely mediated by reduced expression of their transcriptional factors hypoxia-inducible factor-1 and c-Myc. Our results indicate that hyperpolarized (13)C MRSI could potentially detect the molecular effect of various cell signaling inhibitors, thus providing a radiation-free method to predict tumor response.

0 Bookmarks
 · 
116 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cellular components are routinely catalogued by omics-approaches. Methods for interrogating the dynamic function of these components with chemical detail in intact living samples are far less routine. During the last few years, spectroscopy has improved to a level that enables detailed insights into the inner workings of living cells. Due to advances in sensitivity relative to noise and cellular background signals, NMR spectroscopy has recently provided hitherto inaccessible insights into macromolecular structures, chemical environments, dynamic processes and responses to external and internal perturbations in living cells. Here, we detail the progress and emphasize remaining challenges in addressing profound cell biological questions with NMR in living cells.
    Analytical Chemistry 08/2014; 87(1). DOI:10.1021/ac501467x · 5.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Increasing the sensitivity of NMR experiments is an ongoing field of research to help realise the exquisite molecular specificity of this technique. Hyperpolarisation of various nuclei is a powerful approach that enables the use of NMR for molecular and cellular imaging. Substantial progress has been achieved over recent years in terms of both tracer preparation and detection schemes. This review summarises recent developments in probe design and optimised signal encoding, and promising results in sensitive disease detection and efficient therapeutic monitoring. The different methods have great potential to provide molecular specificity not available by other diagnostic modalities. Copyright © 2012 John Wiley & Sons, Ltd.
    NMR in Biomedicine 01/2013; 26(7). DOI:10.1002/nbm.2873 · 3.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Morphological imaging precedes lesion-specific visualization in magnetic resonance imaging (MRI) because of the superior ability of this technique to depict tissue morphology with excellent spatial and temporal resolutions. To achieve lesion-specific visualization of tumors by MRI, we investigated the availability of a novel polymer-based tracer. Although the 13C nucleus is a candidate for a detection nucleus because of its low background signal in the body, the low magnetic resonance sensitivity of the nucleus needs to be resolved before developing a 13C-based tracer. In order to overcome this problem, we enriched polyethylene glycol (PEG), a biocompatible polymer, with 13C atoms. 13C-PEG40,000 (13C-PEG with an average molecular weight of 40 kDa) emitted a single 13C signal with a high signal-to-noise ratio due to its ability to maintain signal sharpness, as was confirmed by in vivo investigation, and displayed a chemical shift sufficiently distinct from that of endogenous fat. 13C-PEG40,000 intravenously injected into mice showed long retention in circulation, leading to its effective accumulation in tumors reflecting the well-known phenomenon that macromolecules accumulate in tumors because of leaky tumor capillaries. These properties of 13C-PEG40,000 allowed visualization of tumors in mice by 13C spectroscopic imaging. These findings suggest that a technique based on 13C-PEG is a promising strategy for tumor detection.
    PLoS ONE 07/2014; 9(7):e102132. DOI:10.1371/journal.pone.0102132 · 3.53 Impact Factor

Full-text (2 Sources)

Download
43 Downloads
Available from
May 27, 2014